Cationic lipid transfection has become the method of choice for delivering genes to most cell types in vitro. The current generation of cationic lipid transfection reagents are effective in vitro because they form stable binary complexes with DNA through electrostatic interactions. After formation these complexes carry a net positive charge which facilitates their interaction with the net negative charge of a cell s plasma membrane. The lack of in vivo transfectability results from a lack of distribution of the transfection competent complexes because of in situ interactions between the positively charged complexes and the negatively charged extracellular matrix components. Phase I specific aims include: 1. Synthesis and physical characterization of variety of novel cationic amphipaths. 2. Characterize in vitro transfectability using standard cell lines in tissue culture. 3. Correlate physical properties and transfection ability with endosomal function and state. 4. Use specific ligands with an indicated cationic liposome formulation to assay for ligand-dependant transfections in tissue culture. PROPOSED COMMERCIAL APPLICATION This new method of non-viral gene delivery will be commercialized by: 1) selling the technology in the form of reagent kits to biomedical and basic researchers 2) licensing the technology for in vivo gene delivery to pharmaceutical companies for the treatment of genetic diseases or acquired diseases 3) licensing the technology for in vivo gene delivery to pharmaceutical companies for vaccine development.